Current paradigms in the management of Philadelphia chromosome positive acute lymphoblastic leukemia in adults. Issue 2 (31st October 2017)

• Record Type: Journal Article
• Authors: El Fakih, Riad; Jabbour, Elias; Ravandi, Farhad; Hassanein, Mona; Anjum, Farhan; Ahmed, Syed; Kantarjian, Hagop
• Is Part Of: American journal of hematology. Volume 93:Issue 2(2018:Feb.)
• Page Start: 286
• Page End: 295
• Publication Date: 2017-10-31
• Subjects: Hematology -- Periodicals; 616.15
• DOI: 10.1002/ajh.24926
• Languages: English
• ISSNs: 0361-8609

Abstract

Abstract: Philadelphia chromosome‐positive (Ph‐positive) acute lymphoblastic leukemia (ALL) is a biologically, clinically, and genetically distinct subtype of precursor‐B ALL. The Ph chromosome, results from a reciprocal translocation of the ABL1 kinase gene on chromosome 9 to the breakpoint cluster region ( BCR ) gene on chromosome 22. Depending on the translocation breakpoint, typically a p210 BCR‐ABL1 or a p190 BCR‐ABL onc protein are generated; both are constitutively active tyrosine kinases that play a central role to alter signaling pathways of cell proliferation, survival, and self‐renewal, leading to leukemogenesis. In Ph‐positive ALL, the p190‐ BCR‐ABL (minor [m]‐bcr) subtype is more frequent than the p210‐ BCR‐ABL (major [M]‐bcr) subtype, commonly found in chronic myeloid leukemia. The Philadelphia chromosome is the most frequent recurrent cytogenetic abnormality in elderly patients with ALL. Its incidence increases with age, reaching ∼50% in patients with ALL aged 60 years and over. Patients traditionally had a very poor outcome with chemotherapy, particularly if they do not undergo allogeneic hematopoietic cell transplantation (allo‐HCT) in first complete remission (CR1). With the availability of multiple tyrosine kinase inhibitors (TKI), the therapeutic armamentarium is expanding quickly. However, there is no consensus on how to best treat Ph‐positive ALL. With modern therapy, improved outcomes have led to the emergence of a number of controversies, including the need for intensive chemotherapy, the ideal TKI, and whether all eligible patients should receive an allo‐HSCT, and if so, what type. Here, we discuss these controversies in light of the available literature.